key: cord-303417-1237ykxt
authors: d’Arminio Monforte, Antonella; Tavelli, Alessandro; Bai, Francesca; Marchetti, Giulia; Cozzi-Lepri, Alessandro
title: Effectiveness of Hydroxychloroquine in COVID-19 disease: A done and dusted situation?
date: 2020-07-29
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.07.056
sha: 
doc_id: 303417
cord_uid: 1237ykxt

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Arshad et al show evidence for a reduced mortality in Covid-19 patients taking hydroxychloroquine alone or with azithromycin in an observational study in USA [1] . Data on effectiveness and toxicity of hydroxychloroquine are controversial [2] [3] [4] [5] [6] .

A total of 539 COVID-19 hospitalised patients were included in our cohort in Milan, from February 24 to May 17,2020 of whom 174 died in hospital (day 14 probability of death: 29.5% -95%CI: 25.5-34.0). We divided a subset of our cohort in three groups who started treatment a median of 1 day after admission: those receiving hydroxycholoroquine alone (N=197), those receiving hydroxycholoroquine+azithromycin (N=94), and those receiving neither (controls) (N=92). Of the latter group, 10 started HIV antivirals (boosted-lopinavir or -darunavir), 1 teicoplanin, 12 immunomodulatory drugs or corticosteroids, 23 heparin and 46 remained untreated. The percent of death in the 3 groups was 27%, 23% and 51%. Mechanical ventilation was used in 4.3% of hydoxychloroquine, 14.2% of hydroxycholoroquine+azithromycin and 26.1% of controls. Unweighted and weighted relative hazards of mortality are shown in Table 1 . After adjusting for a number of key confounders (see table) , the use of hydroxycholoroquine+azithromycin was associated with a 66% reduction in risk of death as compared to controls; the analysis also suggested a larger effectiveness of hydroxychloroquine in patients with less severe COVID-19 disease (PO2/FiO2>300, interaction p-value<.0001). Our results are remarkably similar to those shown by Arshad et al. Some important weaknesses of the analysis by Arshad have been pointed out [7] but not all of these apply to our study. Our propensity scores include some of the potential confounders that were missing in the analysis by Arshad (e.g. calendar day of admission, disease severity, cardio-vascular disease (CVD), baseline plasma CRP); second, we have excluded people receiving other drugs which could have biased the effect of hydroxychloroquine when used in combination. Third, although residual confounding is a possibility (e.g. people with CVD were more frequent in control), people in the control group were more likely to undergo mechanical ventilation that is a conservative bias. These results from two different real-life settings (Italy and USA), are conflicting with those of two large randomised trials [8, 9] . Although unmeasured confounding remains the most likely explanation for the discrepancies, a robust meta-analysis is still lacking and we question whether hydroxychloroquine should be further tested. When best to start treatment is also a question that needs to be addressed in ad-hoc randomised studies. J o u r n a l P r e -p r o o f

Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalised with COVID-19

Hydroxycholoroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomised clinical trial

Hydroxychloroquine in patients mainly with mild to moderate COVID-19: an open-label, randomised, controlled trial

An observational cohort study of hydroxychloroquine and azithromycin for COVID-19: (Can't get no) satisfaction

Effect of desamethasone in hospitalized patients with CVID-19: preliminary report. COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv 9-World Health Organization


